Abstract
Nosocomial infections are produced by pathogens with the ability to persist in hospital environments and with the propensity to develop resistance to diverse antimicrobials. In order to tackle resistance, it has been pointed as good strategy to select resilient drug targets that are evolutionally constrained to design drugs less susceptible to develop resistance. Molecular modeling can help to fulfill this goal by providing a rationalization of the observed resistance at the molecular level and, suggesting modifications on existing drugs or in the design of new ones to overcome the problem. The present report focus on type II topoisomerases, a clinical validated target for antibacterials and describe diverse modes of intervention including, inhibition of their ATPase function, stabilization of the cleavage complex or prevention of DNA strand hydrolysis. Moreover, the origin of resistance is also rationalized on the base of ligand-target interactions. Finally, efforts are described to circumvent the effect of non-susceptible strains by the design of new drugs based on existing ones, like the case of diones that act through the same mechanism as quinolones or the newly released quinole-carbonitrile derivatives that inhibit type II topoisomerases through a new mechanism.
Keywords: Topoisomerases inhibitors, antibiotics design, nosocomial infections, quinolones.
Current Topics in Medicinal Chemistry
Title:Designing Type II Topoisomerase Inhibitors: A Molecular Modeling Approach
Volume: 14 Issue: 1
Author(s): Juan J. Perez, Cecylia S. Lupala and Patricia Gomez-Gutierrez
Affiliation:
Keywords: Topoisomerases inhibitors, antibiotics design, nosocomial infections, quinolones.
Abstract: Nosocomial infections are produced by pathogens with the ability to persist in hospital environments and with the propensity to develop resistance to diverse antimicrobials. In order to tackle resistance, it has been pointed as good strategy to select resilient drug targets that are evolutionally constrained to design drugs less susceptible to develop resistance. Molecular modeling can help to fulfill this goal by providing a rationalization of the observed resistance at the molecular level and, suggesting modifications on existing drugs or in the design of new ones to overcome the problem. The present report focus on type II topoisomerases, a clinical validated target for antibacterials and describe diverse modes of intervention including, inhibition of their ATPase function, stabilization of the cleavage complex or prevention of DNA strand hydrolysis. Moreover, the origin of resistance is also rationalized on the base of ligand-target interactions. Finally, efforts are described to circumvent the effect of non-susceptible strains by the design of new drugs based on existing ones, like the case of diones that act through the same mechanism as quinolones or the newly released quinole-carbonitrile derivatives that inhibit type II topoisomerases through a new mechanism.
Export Options
About this article
Cite this article as:
Perez J. Juan, Lupala S. Cecylia and Gomez-Gutierrez Patricia, Designing Type II Topoisomerase Inhibitors: A Molecular Modeling Approach, Current Topics in Medicinal Chemistry 2014; 14 (1) . https://dx.doi.org/10.2174/1568026613666131113150046
DOI https://dx.doi.org/10.2174/1568026613666131113150046 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Humic Acids as Therapeutic Compounds in Lead Intoxication
Current Clinical Pharmacology Adverse Drug Reactions and Safety Considerations of NSAIDs: Clinical Analysis
Current Drug Safety Non-Invasive Methods of Glucose Measurement: Current Status and Future Perspectives
Current Diabetes Reviews C/EBP Transcription Factors in Lung Disease
Current Respiratory Medicine Reviews Cysteine Proteinases of Trypanosome Parasites Novel Targets for Chemotherapy
Current Drug Targets Structure-Function Relationships of Iodinated Contrast Media and Risk of Nephrotoxicity
Current Medicinal Chemistry Murine Models of Vpr-Mediated Pathogenesis
Current HIV Research The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries
Recent Patents on Cardiovascular Drug Discovery Monoclonal Antibodies as Cancer Therapeutics
Recent Patents on Biotechnology Targeting α7 Nicotinic Acetylcholine Receptor to Combat Inflammation in Cardio-Cerebral-Vascular Diseases
Current Drug Targets The potential for circulating microRNAs in the diagnosis of myocardial infarction: a novel approach to disease diagnosis and treatment
Current Pharmaceutical Design Reactive Oxygen and Nitrogen Species in the Renal Ischemia/Reperfusion Injury
Current Pharmaceutical Design Human Galectin-3 Selective and High Affinity Inhibitors. Present State and Future Perspectives
Current Medicinal Chemistry The Potential Role of Pro-Inflammatory and Anti-Inflammatory Cytokines in Epilepsy Pathogenesis
Endocrine, Metabolic & Immune Disorders - Drug Targets Alternative Gene Therapy Strategies for the Repair of Craniofacial Bone Defects
Current Gene Therapy Cancer Metastasis: Characterization and Identification of the Behavior of Metastatic Tumor Cells and the Cell Adhesion Molecules, including Carbohydrates
Current Drug Targets - Cardiovascular & Hematological Disorders Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer’s disease
Central Nervous System Agents in Medicinal Chemistry MicroRNAs and Peroxisome Proliferator-Activated Receptors Governing the Differentiation of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Anti-Cancer Agent-Induced Nephrotoxicity
Anti-Cancer Agents in Medicinal Chemistry Lung Cancer: Are we up to the Challenge?
Current Genomics